Acyclovir Treatment Window for Herpes Zoster (Shingles)
Acyclovir should be initiated within 72 hours of rash onset for herpes zoster, but treatment started between 48-72 hours still provides significant benefit in reducing pain duration and severity. 1, 2
Standard Treatment Window
The FDA-approved and guideline-recommended window for acyclovir initiation is 72 hours from rash onset, during which the medication accelerates cutaneous healing and reduces acute pain severity 1, 2, 3
Treatment initiated within 48 hours provides superior outcomes compared to treatment started between 48-72 hours, with significantly faster arrest of new lesion formation (p=0.005), loss of vesicles (p<0.001), and full crusting (p=0.02) 4, 5
However, treatment between 48-72 hours remains clinically beneficial for pain reduction, with median time to complete pain resolution of 36-58 days versus longer durations without treatment 6
Evidence Beyond 72 Hours
No clinical trial data exist for treatment initiated more than 72 hours after rash onset in immunocompetent patients, and the FDA label explicitly states this limitation 3
The lack of evidence beyond 72 hours means standard recommendations cannot support routine treatment after this window in otherwise healthy individuals 1, 3
Critical Exception: Immunocompromised Patients
Immunocompromised patients should receive antiviral therapy regardless of timing due to substantially higher risk of disseminated infection and severe complications 2
These patients may require intravenous acyclovir rather than oral formulation, with treatment continuing for a minimum of 7-10 days 2
Clinical Pitfalls to Avoid
Do not confuse the 72-hour window for herpes zoster with the 24-hour window for varicella (chickenpox), which requires much earlier initiation for optimal benefit 7
Do not withhold treatment from patients presenting at 48-72 hours thinking they are "too late"—this window still provides meaningful pain reduction and accelerated healing 6
For patients with severe pain at presentation who receive treatment within 48 hours, 40% achieve no or only mild pain by end of treatment, compared to 0% with placebo (p<0.001) 4
Practical Treatment Algorithm
0-48 hours from rash onset: Initiate acyclovir 800 mg orally five times daily for 7 days—this is the optimal window with maximum benefit 1, 4, 5
48-72 hours from rash onset: Still initiate acyclovir with same dosing—significant benefit persists for pain reduction and healing 6, 5
>72 hours in immunocompetent patients: No evidence supports routine treatment; consider on case-by-case basis for severe presentations 3
Any timepoint in immunocompromised patients: Always treat regardless of timing, consider IV acyclovir for complicated cases 2